Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States.

AIMS: This study assessed the cost-effectiveness of ezetimibe with statin therapy vs statin monotherapy from a US payer perspective, assuming the impending patent expiration of ezetimibe. METHODS: A Markov-like economic model consisting of 28 distinct health states was used. Model population data were obtained from US linked claims and electronic medical records, with inclusion criteria based on diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses, and cost-effectiveness analyses. The base-case scenario was used to evaluate the cost-effectiveness of adding ezetimibe 10 mg to statin in patients aged 35-74 years with a history of coronary heart disease (CHD) and/or stroke, and with low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL over a lifetime horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into account the impending patent expiration in the second quarter of 2017. Sub-group analyses included patients with LDL-C levels ≥100 mg/dL and patients with diabetes with LDL-C levels ≥70 mg/dL. RESULTS: The lifetime discounted incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was $9,149 per quality-adjusted life year (QALY) for the base-case scenario. For patients with LDL-C levels ≥100 mg/dL, the ICER was $839/QALY; for those with diabetes and LDL-C levels ≥70 mg/dL, it was $560/QALY. One-way sensitivity analyses showed that the model was sensitive to changes in cost of ezetimibe, rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base-case and sub-group analyses. LIMITATIONS: Indirect costs or treatment discontinuation estimation were not included. CONCLUSIONS: Compared with statin monotherapy, ezetimibe with statin therapy was cost-effective for secondary prevention of CHD and stroke and for primary prevention of these conditions in patients whose LDL-C levels are ≥100 mg/dL and in patients with diabetes, taking into account a 90% cost reduction for ezetimibe.

Systematic review and meta-analysis of the efficacy of cardioversion by vernakalant and comparators in patients with atrial fibrillation.

PURPOSE: Rate and rhythm control are two well established treatment objectives for atrial fibrillation (AF) patients. While symptom reduction is a primary treatment goal, therapeutic practice related to cardioversion varies by region and patient, with several precautions associated with the use of current therapies. No comprehensive literature review on the relative efficacy of existing cardioversion approaches compared to newly available therapies has been conducted. METHODS AND RESULTS: A systematic literature review and meta-analysis were undertaken to evaluate the efficacy of pharmacologic therapies in eliciting cardioversion within 2 and 8-24 h among patients with recent-onset, short duration AF. Eligible studies included randomized controlled trials in which cardioversion rates were evaluated in at least 2 treatment groups. Bayesian mixed-treatment comparisons estimated odds ratios (95% credible intervals) for successful cardioversion. Results within 2 h showed vernakalant IV, propafenone IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24 h. Few adverse events were reported, with the most common being bradycardia and hypotension. CONCLUSIONS: In pair-wise comparisons of active treatment arms to one another, results suggest vernakalant IV, propafenone IV and flecainide appear to be effective in achieving rapid cardioversion in patients with short duration AF compared to other agents. Application of these findings to clinical practice need to account for the variable comorbidity profiles of patients, important determinants in the selection of appropriate therapy for individual patients. Though best practice methods were used, further research comparing treatments through direct head-to-head comparisons may be warranted to confirm these findings and further inform clinical practice.

Cost-effectiveness of extended-release niacin/laropiprant added to a stable simvastatin dose in secondary prevention patients not at cholesterol goal in Germany.

Coronary heart disease (CHD) remains the leading cause of death in Germany despite statin use to reduce low-density lipoprotein cholesterol (LDL-C) levels; improving lipids beyond LDL-C may further reduce cardiovascular risk. A fixed-dose combination of extended-release niacin (ERN) with laropiprant (LRPT) provides comprehensive lipid management. We adapted a decision-analytic model to evaluate the economic value (incremental cost-effectiveness ratio [ICER] in terms of costs per life-years gained [LYG]) of ERN/LRPT 2 g over a lifetime in secondary prevention patients in a German setting. Two scenarios were modelled: (1) ERN/LRPT 2 g added to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 40 mg; (2) adding ERN/LRPT 2 g compared with titration to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 20 mg. In both scenarios, adding ERN/LRPT was cost-effective relative to simvastatin monotherapy at a commonly accepted threshold of €30,000 per LYG; ICERs for ERN/LRPT were €13,331 per LYG in scenario 1 and €17,684 per LYG in scenario 2. Subgroup analyses showed that ERN/LRPT was cost-effective in patients with or without diabetes, patients aged ≤ 65 or >65 years and patients with low baseline high-density lipoprotein cholesterol levels; ICERs ranged from €10,342 to €15,579 in scenario 1, and from €14,081 to €20,462 in scenario 2. In conclusion, comprehensive lipid management with ERN/LRPT 2 g is cost-effective in secondary prevention patients in Germany who have not achieved LDL-C goal with simvastatin monotherapy.

Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis.

OBJECTIVE: To systematically review and analyse evidence for cholesterol-lowering efficacy of at least 4 weeks of add-on ezetimibe vs doubling statin dose, in adults with primary hypercholesterolaemia. RESEARCH DESIGN AND METHODS: MEDLINE, EMBASE and Cochrane databases were searched to identify randomised controlled trials of ezetimibe-statin combination vs statin titration (January 1993 - March 2010). Studies were selected using predefined criteria. Two reviewers conducted screening of articles, critical appraisal and data extraction; a third reviewer resolved disagreements. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); and proportion of patients achieving LDL-C treatment goal. Data were combined by two sets of direct comparison fixed and random effects meta-analysis: (1) compared data in the same treatment period between groups; (2) compared the incremental change in lipid levels of add-on ezetimibe vs doubling statin dose. Heterogeneity was assessed using the I(2) statistic. RESULTS: Thirteen studies including 5080 patients were included in the meta-analyses. Data on simvastatin, atorvastatin and rosuvastatin were analysed. Results for primary and secondary outcomes were in favour of the ezetimibe-statin combination. A significantly greater percentage reduction in LDL-C levels was achieved in patients treated with ezetimibe-statin vs statin monotherapy (weighted mean difference [WMD]: -14.1% [-16.1, -12.1], p < 0.001). Reduction in LDL-C levels attributed to add-on ezetimibe was significantly greater than that for statin dose doubling (WMD: -15.3% [-19.1, -11.4], p < 0.001). Achievement of LDL-C goal favoured add-on ezetimibe over statin titration and was statistically significant (odds ratio: LDL-C treatment goal 2.45 [1.95, 3.08], p = 0.007). CONCLUSIONS: Meta-analyses were restricted by the limited number of studies with similar trial design and method of statin titration. Results indicate that add-on ezetimibe is significantly more effective in reducing LDL-C levels than doubling statin dose, enabling more patients to achieve LDL-C goal.

[Cost effectiveness in the Danish health care of ezetemibe co-administration compared to simvastatin]. / Omkostningseffektivitet i det danske sundhedsvaesen ved ezetimibe-koadministration med simvastatin.

INTRODUCTION: The purpose of this analysis is to evaluate the cost effectiveness of ezetemibe coadministration compared to a shift to higher doses of simvastatin or to a more potent statin. MATERIALS AND METHODS: The calculations are based on a Markov model in which a patient who does not attain the desired cholesterol outcome with simvastatin treatment is treated either with ezetemibe coadministration, or with increased simvastatin doses, or with a more potent statin. Calculations are conducted for a total of 72 different patient types followed over the remainder of their lives. RESULTS: Ezetemibe coadministration evaluated over the entire lifetime will be somewhat more expensive than simvastatin titration but must, however, be seen in relation to improved survival and increased quality of life. For the typical patient, treatment will be associated with costs of between DKK 50,000 and 100,000 per gained year of life, which cannot be deemed too expensive in relation to other interventions provided by the Health Authorities. For some patient types who receive treatment with a potent statin (atorvastatin), savings will also be possible here as well as an increase in life expectancy and quality of life. CONCLUSION: The results of the study indicate that ezetemibe coadministration is cost effective. The results are sustainable even with quite significant changes of the estimates used and taking into account uncertainties in the material and methods.

Cholesterol reduction yields clinical benefits: meta-analysis including recent trials.

BACKGROUND: Previous meta-analyses reported by Gould et al found significant decreases of 15% in the risk for coronary heart disease (CHD)-related mortality and 11 % in risk for all-cause mortality per decrease of 10% in total cholesterol (TC) level. OBJECTIVE: To evaluate the effects of reducing cholesterol on clinical events after including data from recent clinical trials. METHODS: Using a literature search (MeSH key terms, including: bezafibrate, coronary disease, efficacy, gemfibrozil, hydroxymethylglutaryl-CoA reductase inhibitors, hypercholesterolemia, niacin [nicotinic acids], randomized controlled trials, and treatment outcome; years: 1999-2005), we identified trials published in English that assessed the effects of lipid-modifying therapies on CHD end points, including CHD-related death, myocardial infarction, and angina pectoris. We also included all studies from the previously published meta-analysis. Using the same analytic approach as previously, we determined the effects of net absolute reductions (1 mmol/L [38.7 mg/dL]) in TC and low-density lipoprotein cholesterol (LDL-C) on the relative risks (RRs) for all-cause mortality, CHD-related mortality, any CHD event (mortality or nonfatal myocardial infarction), and non-CHD-related mortality. RESULTS: We included 62 studies involving 216,616 patients, including 126,474 from 24 randomized controlled trials the findings of which were published since the previous meta-analysis (1998). Among all patients, for every 1-mmol/L decrease in TC, there was a 17.5 reduction in RR for all-cause mortality; 24.5 %, for CHD-related mortality; and 29.5% for any CHD event. Corresponding reductions for every 1-mmol/L decrease in LDL-C were 15.6%, 28.0%, and 26.6%, respectively. Similar relationships were observed in patients without CHD. No significant relationship was found between lipid reduction and non-CHD-related mortality risk. CONCLUSIONS: The results from the present analysis support conclusions from previous meta-analyses that cholesterol lowering is clinically beneficial in patients with CHD or at elevated CHD risk. These results also support the previous finding that non-CHD-related mortality is unrelated to lipid reductions.

Projected coronary heart disease risk benefit with ezetimibe.

Low density lipoprotein (LDL) cholesterol and total cholesterol (TC) are the primary clinical parameters of interest for any cholesterol intervention. Clinicians are interested in how the reduction of these lipid parameters as well as increases in high density lipoprotein (HDL) relate to changes in coronary heart disease (CHD) risk. The objective of this analysis was to estimate the additional CHD risk reduction that could potentially be provided by co-administration of ezetimibe with statin therapy. Data from four double-blind placebo controlled clinical trials were used to predict the level of CHD risk reduction that might be achieved by co-administration of ezetimibe with statin therapy when compared to those receiving statin as monotherapy. Patients without a previous history of CHD were included in the analysis. Projected CHD risk reduction was calculated as percent change in projected CHD risk from baseline to 12 weeks based on observed lipid levels at those time points. For all the studies combined greater reductions in percent change in 5-year CHD risk were observed for patients receiving ezetimibe and statin as co-therapy, 53.4%, when compared to those receiving statin alone, 39.7%. Co-administration of ezetimibe with statin therapy provides an additional 13.7% reduction in predicted 5-year CHD risk when compared to statin monotherapy. Reductions in 5-year CHD risk for each of the statin studies ranged from 16.1% for lovastatin to 9.8% for atorvastatin. Co-administration of ezetimibe with statins could significantly reduce CHD events in patients with primary hypercholesterolemia.

The burden of appendicitis-related hospitalizations in the United States in 1997.

BACKGROUND: Acute appendicitis is among the most frequent causes of surgical abdominal disease worldwide. METHODS: Data from the Nationwide Inpatient Sample of the Healthcare Utilization Project were used to estimate the prevalence and disease burden of appendicitis-related hospitalizations in the United States in 1997. The data are a representative sample of discharge records from community hospitals drawn from 22 states in the United States. RESULTS: In the United States in 1997, there were an estimated 252,682 (95% CI: 242,957-262,407) appendicitis-related hospitalizations. The mean length of stay and total charges for appendicitis-related hospitalizations were four days (95% CI: 3.4-4.6) and $11,645 (95% CI: $11,299-$11,992) per hospitalization, respectively. Appendicitis-related hospitalizations associated with post-operative infection, peritoneal abscess, or peritonitis had longer average lengths of stay and higher average costs when compared to hospitalizations associated with local appendicitis without post-operative infection. Appendicitis cases among very young and older patients were more likely to be associated with peritoneal abscess, peritonitis, or post-operative infection. CONCLUSIONS: In 1997, appendicitis-related hospitalizations accounted for 0.6% of all hospitalizations in the United States, resulting in approximately one million hospital days and $3 billion in hospital charges. Between 1984 and 1997, the rate of appendicitis hospitalizations in the U. S. population declined slightly, whereas the total number of hospital days remained unchanged.

The effect of montelukast versus usual care on health care resource utilization in children aged 2 to 5 years with asthma.

BACKGROUND: Limited clinical data are available on the long-term effects of asthma controller therapy on the utilization of health care resources in pediatric patients with asthma. OBJECTIVE: The objective of this study was to compare the effects of long-term treatment with montelukast and usual care on health care resource use in children with asthma. METHODS: Pediatric patients aged 2 to 5 years with asthma who had completed a 3-month, double-blind, double-dummy clinical trial comparing montelukast 4 mg and placebo were asked to participate in an open-label, controlled extension study comparing montelukast 4 mg and usual care. Usual care was defined as cromolyn or inhaled corticosteroid therapy Health care resource utilization was measured in terms of oral corticosteroid use and numbers of physician visits, emergency department visits, and hospitalizations. RESULTS: Of 618 patients who completed the primary phase of the study, 516 (83.5%) participated in the extension study Data from 506 patients (302 without previous asthma maintenance therapy, 204 with) were included in the analysis. During the extension phase, patients who received montelukast and had not used previous asthma maintenance therapy were followed for a mean of 329.5 days; those who received usual care and CONCLUSION: In this open-label study, pediatric patients aged 2 to 5 years with mild to moderate persistent asthma receiving long-term therapy with montelukast had similar rates of asthma-related health care resource utilization compared with those receiving usual care with cromolyn or inhaled corticosteroids.